Precautions of Palbociclib

1 Neutropenia 

Neutropenia was the most frequently reported adverse reaction in Study 1 (PALOMA-2) with an  incidence of 80% and Study 2 (PALOMA-3) with an incidence of 83%. A Grade ≥3 decrease in  neutrophil counts was reported in 66% of patients receiving Palbociclib plus letrozole in Study 1 and 66% of patients receiving Palbociclib plus fulvestrant in Study 2. In Study 1 and 2, the median time to  first episode of any grade neutropenia was 15 days and the median duration of Grade ≥3 neutropenia  was 7 days.

Monitor complete blood counts prior to starting Palbociclib therapy and at the beginning of each cycle,  as well as on Day 15 of the first 2 cycles, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Febrile neutropenia has been reported in 1.8% of patients exposed to Palbociclib across Studies 1 and 2.  One death due to neutropenic sepsis was observed in Study 2. Physicians should inform patients to  promptly report any episodes of fever.

2 Interstitial Lung Disease (ILD)/Pneumonitis 

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients  treated with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including Palbociclib when taken in  combination with endocrine therapy.

Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of Palbociclib-treated patients had  ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4 and no fatal cases were reported. Additional  cases of ILD/pneumonitis have been observed in the postmarketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g. hypoxia, cough,  dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have  developed pneumonitis, interrupt Palbociclib immediately and evaluate the patient. Permanently  discontinue Palbociclib in patients with severe ILD or pneumonitis.

3 Embryo-Fetal Toxicity  

Based on findings from animal studies and its mechanism of action, Palbociclib can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of palbociclib  to pregnant rats and rabbits during organogenesis resulted in embryo-fetal toxicity at maternal exposures  that were ≥4 times the human clinical exposure based on area under the curve (AUC). Advise pregnant  women of the potential risk to a fetus. Advise females of reproductive potential to use effective  contraception during treatment with Palbociclib and for at least 3 weeks after the last dose.

from FDA，2022.12